Cancer risk associated with chronic diseases and disease markers: prospective cohort study

Abstract

Objectives: To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers.

Design: Prospective cohort study.

Setting: Standard medical screening program in Taiwan.

Participants: 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years.

Main outcome measures: Cancer incidence and cancer mortality.

Results: A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk associated with chronic diseases and markers was attenuated by 48% for cancer incidence and 27% for cancer mortality.

Conclusions: Chronic disease is an overlooked risk factor for cancer, as important as five major lifestyle factors combined. In this study, chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death. Physical activity is associated with a nearly 40% reduction in the cancer risk associated with chronic diseases.

Fig 1

Chronic diseases and markers and risk of incident cancer. *Adjusted for age (continuous), age squared, sex, education (middle school or lower, high school, junior college, or college or higher), occupation (white collar, blue collar, self employed, housewife or house husband, or other), smoking status (never, former, or current), pack years of smoking (continuous), alcohol consumption status (never, ever), grams of alcohol/day (continuous), body mass index (continuous), body mass index squared, physical activity (inactive, low active, medium active, high active, and very high active), and fruit and vegetable intake (continuous). †All chronic diseases and markers were simultaneously included in the model in addition to the covariates

Fig 2

Chronic diseases and markers and risk of cancer death. *Adjusted for age (continuous), age squared, sex, education (middle school or lower, high school, junior college, or college or higher), occupation (white collar, blue collar, self employed, housewife or house husband, or other), smoking status (never, former, or current), pack years of smoking (continuous), alcohol consumption status (never, ever), grams of alcohol/day (continuous), body mass index (continuous), body mass index squared, physical activity (inactive, low active, medium active, high active, and very high active), and fruit and vegetable intake (continuous). †All chronic diseases and markers were simultaneously included in the model in addition to the covariates

Fig 3

Chronic disease risk score and risk of incident cancer and cancer death overall and stratified by physical activity. Numbers at bottom of graphs represent adjusted hazard ratios (95% confidence intervals) adjusted for age (continuous), age squared, sex, education (middle school or lower, high school, junior college, or college or higher), occupation (white collar, blue collar, self employed, housewife or house husband, or other), smoking status (never, former, or current), pack years of smoking (continuous), alcohol consumption status (never, ever), grams of alcohol/day (continuous), body mass index (continuous), body mass index squared, physical activity (inactive, low active, medium active, high active, and very high active), and fruit and vegetable intake (continuous), wherever appropriate. Physically inactive: <3.75 metabolic equivalent (MET) hours/week; physically active: ≥3.75 MET hours/week. The relative reduction in risk of incident cancer and cancer death associated with chronic diseases or disease markers by physical activity was calculated as (hazard ratio_inactive-hazard ratio_active)/(hazard ratio_inactive-1)×100, where hazard ratio_inactive is the hazard ratio of chronic diseases/markers among those who were physically inactive, and hazard ratio_active is the hazard ratio among those who were physically active

Fig 4

Adjusted hazard ratios associated every increment of five chronic disease risk scores for cancer incidence and cancer mortality of overall cancers and specific cancers. *Hazard ratios were adjusted for age (continuous), age squared, sex, education (middle school or lower, high school, junior college, or college or higher), occupation (white collar, blue collar, self employed, housewife or house husband, or other), smoking status (never, former, or current), pack years of smoking (continuous), alcohol consumption status (never, ever), grams of alcohol/day (continuous), body mass index (continuous), body mass index squared, physical activity (inactive, low active, medium active, high active, and very high active), and fruit and vegetable intake (continuous)

Fig 5

Years of life lost associated with chronic disease risk score, individual chronic disease or marker, and lifestyle risk factors among men and women. Physically inactivity refers to <3.75 metabolic equivalent hours/week, and low fruit and vegetable intake refers to <2 portions/day

Fig 6

Population attributable fractions of cancer incidence due to chronic diseases or markers and lifestyle risk factors. Abnormal glomerular filtration rate=<60 or ≥90 mL/min/1.73 m²; abnormal uric acid level=<416 or ≥476 µmol/L; high heart rate=≥70 beats/min; low total cholesterol level=<4.15 or 4.15-4.66 mmol/L; smoking=ever smoking; insufficient physical activity refers to levels that do not meet current leisure time physical activity recommendation of 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity (ie, <7.50 metabolic equivalent hours/week) ; insufficient fruit/vegetable intake refers to <5 portions/day recommended by the Word Health Organization; alcohol consumption refers to ever alcohol consumption; non-ideal body mass index refers to body mass index of more than 21.9 kg/m², which was the mean body mass index in the normal body mass index (18.5-24.9) category in this study population

Fig 7

Population attributable fractions of cancer mortality due to chronic diseases or markers and lifestyle risk factors. Abnormal glomerular filtration rate=<60 or ≥90 mL/min/1.73 m²; abnormal uric acid level=<416 or ≥476 µmol/L; high heart rate=≥70 beats/min; low total cholesterol level=<4.15 or 4.15-4.66 mmol/L; smoking=ever smoking; insufficient physical activity refers to levels that do not meet current leisure time physical activity recommendation of 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity (ie, <7.50 metabolic equivalent hours/week) ; insufficient fruit/vegetable intake refers to <5 portions/day recommended by the Word Health Organization; alcohol consumption refers to ever alcohol consumption; non-ideal body mass index refers to body mass index less than or more than 25.6 kg/m², which was associated with the lowest risk of cancer mortality in this study